Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury DOUGLAS K. ANDERSON, PH.D., LEON D. PROCKOP, M.D., EUGENE D. MEANS, M.D., AND LAWRENCE E. HARTLEY, B.S.
Research Service, Veterans Administration Hospital. and Department of Physiology and Neurology Section, Department of Medicine, University of South Florida College of Medicine, Tampa, Florida v' Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Cat*), magnesium (Mg~+), and chloride (C1) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca ++ concentration on Days 3, 9, 11, 13, and 15, elevation in K + concentration on Days 9 and 11 and decline in C1 levels on the first day. The CSF K + increase probably reflected cellular loss of K* from damaged tissue whereas the Ca ++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury. KEY WORDS 9 spinal cord injury lactate electrolytes
T is now generally agreed that cerebrospinal fluid (CSF) is in direct equilibrium with and reflects the composition of the central nervous system (CNS) extracellular fluid (ECF). 4,7,8 Thus, analysis of C S F can provide an index of C N S metabolism in normal and diseased states. Examination of various CSF components has been used to provide direct diagnosis of a number of clinical conditions, 2t,22 and to determine prognosis of and to guide therapy in cerebral disease or injury? ,12,~8,~8,2~For ex-
I
J. Neurosurg. / Volume 44 / June, 1976
9 cerebrospinal fluid
9
ample, CSF lactate levels are elevated after head injury 3,1~ and may reflect the degree of cerebral damage? 2 With the exception of a study by Bulat, et al., 2 describing a decline in lumbar CSF concentrations of 5-hydroxyindolacetic acid 19 days after spinal cord trauma in cats, no investigative work in this area concerning spinal cord disease or injury has previously been performed. Recent reports of lactate a4 and electrolyte iS alterations in injured spinal cord tissue suggest that CSF analysis following spinal cord 7]5
D. K. Anderson, et al. trauma might be useful in the further study of spinal cord metabolic and/or biochemical changes attending spinal cord injury. The present studies were performed to determine whether experimental spinal cord compression caused significant changes in CSF lactate and electrolyte levels. Methods and Materials
For this study we used immunized and conditioned female mongrel cats ranging in weight from 2.3 to 4.6 kg. They were divided into two groups: one group underwent experimental injury and the other comprised operative controls.
Experimental Injury Animals
intramuscular procaine penicillin (22,000 units/kg) on the day of surgery, and then every other day for 1 week postoperatively. In addition, the animals were given subcutaneous 5% dextrose in Ringer's solution (10 cc/kg) daily postoperatively until they were alert and feeding. With this model, either reversible or irreversible paraplegia can be produced depending upon the magnitude of the weight and the duration of compression. For this study reversible paraplegia was produced by a 5-minute compression with 170-gm weight. The injury was characterized by varied return of weight-bearing and walking 2 to 4 weeks post injury. This magnitude of weight and duration of compression was chosen because it allowed repeated withdrawals of CSF from the lumbar subarachnoid space and eliminated subarachnoid bleeding.
All animals were anesthetized with intraperitoneal (IP) pentobarbital sodium (40 mg/kg) and intubated to maintain a patent airway. A polyethylene cannula was placed in Control Animals the abdominal aorta by way of a femoral In another group of animals designated arteriotomy in order to monitor blood operative controls, all procedures just pressure and to obtain samples for blood gas described were performed with the exception and pH analysis. Ventilation was not assisted of spinal cord compression. unless abnormal blood gas and pH values were obtained. A femoral vein was canCerebrospinal Fluid Sampling nulated for administration of supplemental doses of anesthesia and other drugs as Samples of CSF were obtained from the necessary. Rectal temperature was measured, lumbar subarachnoid space just before and and body temperature maintained between after laminectomy (operative controls) or 36 ~ and 38 ~ C with a heating pad. The cats spinal cord injury (experimental group). were immobilized in a stereotaxic frame, a Postoperative samples in both groups were one-segment laminectomy was performed at obtained at 48-hour intervals starting at 24 L-2, and the epidural fat was removed to ex- hours and continuing for 17 to 21 days. All pose the dura mater. Spinal cord trauma was postoperative CSF samples were obtained induced using a modification of the compres- with the animals lightly anesthetized with insion model described by Waggenexa6 and tramuscular ketamine hydrochloride (10 Richardson and Nakamura. ~8 This method mg/kg). With the animals in a "sphinx-like" involved placing a known weight, ex- position and secured in a stereotaxic frame, tradurally, on the spinal cord for a prescribed the lumbar subarachnoid space was entered length of time. The injury apparatus was a by percutaneous puncture with a shortstainless steel rod (tip, 6 mm in diameter) that beveled No. 20 needle between L-6 and L-7. could be weighed as desired. The rod passed The CSF samples were immediately centhrough a guide tube which was carefully trifuged to remove any blood that might be positioned directly over and perpendicular to present and refrigerated at 4 ~ C until the center of the spinal cord thereby produc- analyzed. It was determined that "slightly ing compression. Succinycholine chloride (1 tinged" CSF samples (hematocrit of 2% or mg/kg) was administered intravenously just less) had no effect on CSF lactate or elecprior to compression to prevent movement trolyte levels if centrifuged immediately. once compression was initiated. All animals Grossly bloody samples were discarded. All were mechanically ventilated during this samples were analyzed within 48 hours for period of muscle paralysis. The wound was lactate, sodium (Na+), potassium (K+), closed in layers and the animals were given calcium (Ca++), magnesium (Mg§ and 716
J. Neurosurg. / Volume 44 / June, 1976
C S F l a c t a t e a n d e l e c t r o l y t e s in c o r d i n j u r y
FIG. 1. Lactate (mg/100 ml, ordinate) concentrations in CSF plotted as a function of days (abscissa) following spinal cord compression (solid line) or laminectomy (broken line). All values are means and vertical bars indicate standard error of the mean (SEM). N = normal (prelaminectomy) or injury CSF lactate concentrations.
chloride (CI). In addition, total protein was analyzed in a limited number of samples. Lactate was determined by the lactate dehydrogenase method, 1 Na +, K +, Ca ++, and Mg §247 by atomic absorbance, C1 by automatic chloride titrator, and protein by the Lowry modification of the FolinCiocalteau procedure? 5
Statistical Analysis All biochemical data obtained were statistically analyzed by the Mann-Whitney U test. Table 1 and Figs. 1 to 4 express the results as group means (as a summary statistic) together with the standard errors of the mean (SEM). A probability of 0.05 was used as the minimum level of significance. Results
Lumbar CSF lactate, Na +, K § Ca ++ , Mg ++, and CI concentrations were determined at 48-hour time intervals for 17 to 21 days following either laminectomy and spinal cord compression (experimental) or laminectomy only (control). Table 1 is a summary of the data appearing in Figs. 1 to 4 for both experimental and control animals. In addition, normal values (means + SEM) for lactate and electrolytes
J. Neurosurg. / Volume 44 / June, 1976
FIG. 2. Sodium (open squares) and chloride (open circles) concentrations (mEq/1, ordinate) in CSF plotted as a function of days (abscissa) post injury (experimental) or laminectomy (control). N = normal CSF sodium and chloride levels.
have been included along with percentage changes from normal at each sampling interval for both control and experimental CSF lactate levels.
Lactate Levels Data reported in Fig. 1 (solid line) and Table 1 reveal significant increases in CSF lactate levels on Days 1 through 9 post injury with peak levels (50% above normal) occurring at Day 5. In control animals (broken line), CSF lactate levels were significantly reduced by 24 hours post laminectomy and remained depressed throughout the 2- to 3-week experimental period. In these cats CSF lactate concentrations were reduced between 15% and 22% below normal (Table 1). There were significant differences between control and experimental CSF lactate concentrations at every sampling interval throughout the experiment.
Electrolyte Levels There was no significant difference between control and experimental CSF Na § levels at any sampling interval throughout the experimental period, although there was a tendency for Na + to be elevated at 11 days post injury (Fig. 2, open squares; Table 1). A
717
D. K. Anderson, et al. TABLE 1
Normal and postinjury CSF lactate and electrolyte values Substance lactate (normal values = ~- SEM) 13.5 • 0.4 N = 27 sodium (normal values • SEM) 157.1 • 0.5 N = 27 chloride (normal values • SEM) 137.9 • 0.3 N = 27 potassium (normal values ~- SEM 2.8 • 0.02 N = 27 calcium (normal values 2~ ~- SEM 2.8 • 0.04 N = 27 magnesium (normal values ~- SEM) 1.9 • 0.02 N = 24
=
Days Postop *
Units
Group
mg/lO0 ml
experimental
1
control mEq/l
experimental control
=
mEq/l
experimental control
=
mEq/1
experimental control
=
mEq/1
experimental control
=
mEq/1
experimental control
3
2~ • SEM ~o change from normal N • SEM change from normal N • SEM N
16.0 • 1.1 18.5 12 10.8 • 0.8 --20.0 5 155.8 • 0.9 11
17.9 • 0.8 32.6 8 10.7 • 0.5 --20.7 6 157.4 • 0.7 5
2~ • SEM N • SEM N
157.8 • 0.2 4 134.4 • 1.0 8
158.4 • 1.3 5 137.2 • 0.9 6
• SEM N • SEM N
139.5 • 0.6 4 2.8 • 0.05 10
137.0 • 0.4 4 3.0 • 0.05 8
• SEM N • SEM N
2.8 • 0.03 4 2.9 • 0.04 10
3.0 • 0.09 5 3.2 • 0.07 7
• SEM N • SEM N
2.9 • 0.09 4 1.9 • 0.04 9
2.9 • 0.06 6 1.9 • 0.04 7
• SEM N
-
1.8 • 0.0 3
* Includes both laminectomy plus injury (experimental) and laminectomy only (controls). All values are means (X) • standard errors of the mean (SEM); N = number of animals.
FIG. 3. P o t a s s i u m c o n c e n t r a t i o n s in ( m E q / l , ordinate) versus days following cord compression (injury) or l a m i n e c t o m y trol). N = p r e i n j u r y or l a m i n e c t o m y potassium values. 718
CSF spinal (conCSF
s i g n i f i c a n t r e d u c t i o n a t 24 h o u r s w a s t h e o n l y d e m o n s t r a b l e c h a n g e in C S F C I levels p o s t i n j u r y ( F i g . 2, open circles; T a b l e 1). Levels of CSF K § were significantly e l e v a t e d a b o v e n o r m a l o n D a y s 3 t h r o u g h 13 p o s t i n j u r y ( F i g . 3, solid line," T a b l e 1). However, CSF K § concentrations from control animals were also significantly elevated o n D a y s 3 t h r o u g h 7 ( F i g . 3, broken line," T a b l e 1) a n d t h e o n l y s i g n i f i c a n t d i f f e r e n c e between experimental and control CSF K § levels o c c u r r e d o n D a y s 9 a n d 11. D a t a r e p o r t e d in Fig. 4 (open squares, solid line) a n d T a b l e 1 d i s c l o s e a s i g n i f i c a n t inc r e a s e in C S F C a +§ levels o n D a y s 3 t h r o u g h 13 p o s t i n j u r y . A l t h o u g h c o n t r o l C S F C a §247 concentrations were slightly elevated on postl a m i n e c t o m y D a y s 3 t h r o u g h 11, n o n e o f t h e s e i n c r e a s e s w e r e s i g n i f i c a n t ( F i g . 4, open
J. Neurosurg. / Volume 44 / June, 1976
CSF lactate and electrolvte8 in cord injury TABLE 1
5
(Continued)
D a y s Postop* 11
7
9
20.1 J: 1.0 48.9 11 10.9 • 0.5
17.8 • 1.0 31.9 10 11.0 • 0.5
17.4 • 1.2 28.9 9 10.6 • 0.4
16.5 • 1.5 22.2 6 11.4 • 0.3
15.4 • 0.8 14.1 7 11.5 • 0.3
13.5 = 0.7 0 5 11.0 • 0.3
-- 19.3
-- 18.5
-- 21.5
-- 15.6
-- 14.8
-- 18.5
5 157.7 • 1.2 12
6 156.9 ~: 1.0 10
6 158.6 • 1.0 9
6 160.6 • 1.4 7
5 158.9 ~: 1.1 7
5 157.0 • 1.1 4
14.6 • 1.0 8.1 3 11.3 • 0.2 - - 16.3 5 158.0 • 0 3
158.0 •
1.9 5 138.0 ~- 1.0 8
155.8 •
1.4 4 138.8 • 1.6 5
157.2 •
1.5 6 138.7 = 0.8 6
157.2 • 1.9 6 139.0 • 1.5 4
156.4 =L 1.4 5 137.8 • 1.3 4
158.0 ~: 1.0 5 139.0 1
157.0 • 1.8 5 138.0 1
138.0 • 0.3 5 2.9 • 0.04 12
137.0 •
3.0 • 0.04 10
139.0 • 0.6 3 3.1 • 0.09 9
138.3 • 0.9 3 3.2 ~= 0.08 7
138.0 =a 0.9 5 3.0 = 0.07 7
138.0 • 0.4 5 2.9 i 0.07 4
138.6 • 0.2 5 3.0 • 0.07 3
3.0 • 0.08 6 3.1 = 0.08 10
2.9 • 0.05 6 3.1 =~ 0.06 10
3.0 =~ 0.05 5 3.1 • 0.07
2.9 • 0.02 5 3.0 • 0.06
2.9 • 0.02 5 2.9 ~ 0.1
3.0 • 0.06 5 3.0 • 0.06
2.9 • 0.07 5 1.9 • 0.04 9
3.0 • 0.09 6 1.9 • 0.06 9
2.9 • 0.06 6 2.0 • 0.05 8
2.9 • 0.08 5 1.9 • 0.04 7
2.8 • 0.04 5 1.8 • 0.06 7
2.6 • 0.05 5 1.9 ~ 0.09 4
2.7 • 0.1 5 1.9 • 0.07 3
2.0 = 0.09 3
1.9 • 0.05 4
2.1 • 0.03 6
2.1 ~- 0.05 5
2.0 • 0.03 5
1.9 • 0.03 5
1.9 ~= 0.02 5
2.9 • 0.1 5 3.0 • 0.07 11
1.2 4
7
13
7
15
4
17
3
squares, broken line).
Significant differences b e t w e e n e x p e r i m e n t a l a n d c o n t r o l C S F C a ++ l e v e l s w e r e n o t e d o n D a y s 3, 9, 11, 13, a n d 15 ( F i g . 4 a n d T a b l e 1). L e v e l s o f C S F M g ++ w e r e n o t s i g n i f i c a n t l y altered at any postinjury sample interval (Fig. 4, open triangles, solid line). H o w e v e r , v a r i a t i o n s in c o n t r o l C S F M g ++ l e v e l s ( F i g . 4, open triangles, broken line) r e s u l t e d in significant elevations of this ion on postlaminectomy D a y s 3 t h r o u g h 13. C o n s e quently, significant differences between control and experimental C S F M g ++ l e v e l s o c c u r r e d o n D a y s 9 a n d 11 ( F i g . 4 a n d T a b l e 1).
Discussion
Lactate Levels Our results demonstrated a significant rise in C S F c o n c e n t r a t i o n s o f l a c t a t e b y 2 4 h o u r s
J. Neurosurg. / Volume 44 /June, 1976
Fro. 4. P o s t i n j u r y C S F c a l c i u m (open squares) a n d m a g n e s i u m (open triangles) c o n c e n t r a t i o n s ! m E q / l , o r d i n a t e ) as a f u n c t i o n o f d a y s f o l l o w i n g injury or l a m i n e c t o m y . N = n o r m a l or p r e s u r g e r y ( l a m i n e c t o m y p l u s c o m p r e s s i o n or l a m i n e c t o m y only.) C S F c a l c i u m a n d m a g n e s i u m c o n c e n trations. 719
D. K. A n d e r s o n , e t al. post injury which remained elevated above normal values for 9 days. The average peak increase in CSF lactate levels occurred at 5 days post injury and thereafter declined toward normal. There is general agreement that: 1) there are considerable blood-brain and blood-CSF barriers to lactate; ~'17'~~ 2) CSF lactate finds its origin in nervous tissue and not in blood; s~ and 3) CSF lactate levels reflect CNS extracellular fluid lactate levels. 1~ Therefore, the increases in CSF lactate seen in this study indicate a shift in injured spinal cord tissue metabolism toward anaerobiosis due to hypoxia. The prolonged elevation of CSF lactate suggests a continuing hypoxia of metabolically active spinal cord tissue for several days post injury. It has been reported that pO2 levels 8'9 decline in injured spinal cord tissue of experimental animals. In addition, a decrease in blood flow through central gray matter of traumatized spinal cord tissue has been demonstrated? ,~ Although not measured in our study, a decrease in blood flow through the injured area (with resulting hypoxia and perhaps also decreased "washout") is probably responsible for the elevated CSF lactate levels observed. The long-term elevation of CSF lactate is at variance with results reported by Locke, et al. TM After a 300-gm-cm impact injury in monkeys, they excised traumatized and nontraumatized (control) segments of spinal cord tissue at nine different time intervals (one monkey/time interval) ranging between 1.5 minutes and 48 hours post injury. These workers demonstrated elevated lactic acid concentrations in traumatized segments of spinal cord for 12 to 18 hours following injury, and concluded that the lactic acid increase presumably resulted from decreased oxygenation and perfusion. At 18 hours post injury, tissue lactate levels approximated control values. The reasons for the discrepancy between our data and those of Locke, et al., 14 might include: 1) different methods of injury, that is, impact versus compression; 2) differences in the magnitude of injury; and 3) species differences. A slight delay between lactate release by hypoxic spinal cord tissue and its appearance in lumbar CSF may occur. This, however, could not account solely for the long-term (9-day) elevation in postinjury CSF lactate levels seen in our study. It has been demonstrated that edema is a secondary posttraumatic complication of ex720
perimental spinal cord injury. 8,18,28 Lewin, et al.? ~ found an increased tissue water content
(edema) 1 day following impact spinal cord trauma in cats. Edema was maximum between Days 3 through 6 and had begun to decline by Day 9. Yashon, et al.? 8 reported evidence of edema 5 minutes after injury which persisted for 15 days reaching a maximum at 5 days following impact trauma to the spinal cord of monkeys. They concluded that since Locke, et al., ~" found evidence of hypoxia (elevated tissue lactate levels) for only 18 hours post injury, long-term edema was due primarily to other factors. Our data imply that posttraumatic hypoxia of the spinal cord is of a long duration. Thus, the long-lasting edema reported by others~8 may be dependent, at least in part, on hypoxia. Taylor and Crockard ~5 indicate that serial CSF lactate levels can rise due to an expanding intracranial hematoma or increasing localized edema following head injury. Since the spinal cord is contained within the relatively inelastic pia mater, it has been proposed that the increased tissue volume raises the pressure on spinal cord tissue resulting in a secondary compression of parenchymal structures. 28 Perhaps edema with resulting compression of spinal tissue vascular elements might contribute to the long-term hypoxia seen in this study. Further investigation of these questions is required before any definitive conclusions can be drawn. The decrease in CSF lactate levels following laminectomy in the control animals was an unexpected, but consistent, finding. Several possibilities could explain this observation. These include: 1) a laminectomyinduced decrease in glucose utilization; 2) increase in oxygen extraction; or 3) increase in spinal cord tissue perfusion that increases "washout" and/or shifts tissue metabolism toward aerobiosis due to increased oxygen delivery to spinal cord tissue. Studies designed to determine which mechanisms are involved are currently in progress in our laboratory. It is hoped that changes in CSF lactate levels will demonstrate a positive correlation with the degree of neurological deficit and return of neurological function in future animal studies and in human patients with spinal cord injuries. Lactate levels in CSF might then be of prognostic value and may J. Neurosurg. / Volume 44 / J u n e , 1976
C S F l a c t a t e a n d e l e c t r o l y t e s in c o r d i n j u r y segments 6 and 9 days following impact injury. They concluded that the K + loss was due to necrotic as well as edematous changes in Electrolyte Levels the injured cord. Thus, the significant CSF The only changes in CSF electrolyte com- K + elevations seen on Days 9 and 11 post inposition that can be attributed to spinal cord jury are probably a reflection of this K § loss trauma p e r se were significant elevations from injured tissue. Correlative histopathological findings in above levels in control animals of Ca ++ concentrations on postinjury Days 3, 9, 11, 13, our laboratory are similar in many respects to and 15, and in K § concentrations on postin- those described in impact injury 5,27 and jury Days 9 and 11. Chloride levels in CSF suggest a common pathogenic mechanism. were significantly reduced below those in con- These findings include hemorrhagic necrosis trol animals at 24 hours post injury. Changes of gray matter, microvacuolation and in CSF electrolytes were minor, amounting to ischemic nerve cell change of anterior horn only a 0.2 to 0.3 m E q / l elevation for K § and cells, "edematous" changes in white matter, Ca § and a 5 mEq/l decline for CI . It may and subsequent cavitation of the spinal cord be that the injured spinal cord segment was involving gray and white matter with relative too small to be reflected in larger alterations sparing of dorsal columns. These histological of CSF electrolyte composition, especially findings will be described in detail in a after dilution within the CSF compartment. separate report. The presence of active clearance mechanisms for K § from the subarachnoid space may Acknowledgments have also played a role in keeping the concenThe authors would like to thank Ms. Dianne tration of this ion near normal values." Kikta, Gail Trocki, and Lisa Kalaf for their It is known that Ca § binds to protein and valuable technical assistance and also Ms. Robin increased Ca §247concentrations have been Scott for typing the manuscript. noted in CSF with elevated protein levels. 2~ While protein levels were not determined in References all samples, periodic analysis revealed that 1. Beutler E: Red Cell Metabolism. A Manual of CSF protein levels were slightly elevated Biochemical Methods. New York: Grune & above normal (60 to 75 mg/100 ml) at various Stratton, 1971, pp 109-111 intervals post trauma. The postinjury eleva2. Bulat M, Lackovi6 Z, Jakup~evi~ M: 5tion of CSF Ca §247may, therefore, be a conhydroxyindoleacetic acid in the lumbar fluid: a sequence of increased CSF protein levels. specific indicator of spinal cord injury. Science Cerebrospinal fluid CI levels can be secon185:527-528, 1974 3. Crockard HA, Taylor AR: Serial CSF lacdarily decreased in the presence of increased tate/pyruvate values as a guide to prognosis in CSF protein 2~or HCO-3? 4 Whether this is the head injury coma, in Fieschi C (ed): Cerebral basis for the decline in CSF C1 concentration Blood Flow and Intracranial Pressure. New at 24 hours post injury is unknown. Perhaps York: S Karger, 1972, pp 533-539 postinjury decline in CSF C1 was due to 4. Davson H: Physiology of the Cerebrospinal other unknown factors. Fluid. Boston: Little, Brown, 1967 Potassium levels in CSF were significantly 5. Ducker TB, Kindt GW, Kempe LG: elevated above normal values on Days 3 Pathological findings in acute experimental through 13 post injury, as were the CSF K + spinal cord trauma. J Neurosurg 35:700-708, concentrations from control animals on Days 1971 6. Ducker TB, Lucas J: Recovery from spinal 3 through 7 post laminectomy. The increase cord injury, in Seeman P, Brown GM (eds): in CSF K + values for the first postoperative Frontiers in Neurology and Neuroscience week in both control and experimental Research. Toronto: University of Toronto animals may have been the result of nonPress, 1974, pp 142-154 specific tissue damage from repeated lumbar 7. Fencl V, Miller TB, Pappenheimer JR: punctures. The only elevations in CSF K + Studies on the respiratory response to disturthat might be attributed to the injury per se bances of acid-base balance, with deductions occurred on Days 9 through 11 post injury. concerning the ionic composition of cerebral Lewin, et al., la found a net loss of K § from interstitial fluid. Am J Physiol 210:459-472, both injured and adjacent spinal cord 1966 provide an index to the efficacy of various therapeutic modalities.
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D. K. Anderson, et al. 8. Katzman R, Pappius HM: Brain Electrolytes and Fluid Metabolism. Baltimore: Williams & Wilkins, 1973 9. Kelly DL Jr, Lassiter KRL, Calogero JA, et al: Effects of local hypothermia and tissue oxygen studies in experimental paraplegia. J Neurosurg 33:554-563, 1970 10. King LR, McLaurin RL, Knowles HC Jr: Acid-base balance and arterial and CSF lactate levels following human head injury. J Neurosurg 40:617-625, 1974 11. Kobrine AI, Doyle TF, Martins AN: Local spinal cord blood flow in experimental traumatic myelopathy. J Neurosurg 42: 144-149, 1975 12. Kurze T, Tranquada RE, Benedict K: Spinal fluid lactic acid levels in acute cerebral injury, in Caveness WS, Walker AE (eds): Head Injury. Philadelphia: JB Lippincott, 1966, pp 254-259 13. Lewin MG, Hansebout RR, Pappius HM: Chemical characteristics of traumatic spinal cord edema in cats. Effect of steroids on potassium depletion. J Neurosurg 40:65-75, 1974 14. Locke GE, Yashon D, Feldman RA, et al: Ischemia in primate spinal cord injury. J Neurosurg 34:614-617, 1971 15. Lowry OH, Rosebrough NJ, Farr AL, et al: Protein measurement with the folin-phenol reagent. J Biol Chem 193:265-275, 1951 16. Moir ATB, Ashcraft GW, Crawford TBB, et al: Cerebral metabolites in cerebrospinal fluid as a biochemical approach to the brain. Brain 93:357-363, 1970 17. Plum F, Posner JB: Blood and cerebrospinal fluid lactate during hyperventilation. Am J Physiol 212:864-870, 1967 18. Posner JB, Plum F: Spinal fluid pH and neurologic symptoms in systemic acidosis. N Engl J Med 277:605-613, 1967 19. Prockop LD: Cerebrospinal fluid lactic acid. Clearance and effect on facilitated diffusion of a glucose analogue. Neurology 18:189-196, 1968 20. Prockop LD: Disorders of cerebrospinal fluid and brain extracellular fluid, in Gaull GE (ed):
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Biology of Brain Dysfunction. New York: Plenum Press, 1973, pp 229-264 21. Prockop LD, Fishman RA: Experimental pneumococcal meningitis. Permeability changes influencing the concentration of sugars and macromolecules in cerebrospinal fluid. Arch Neurol 19:449-463, 1968 22. Quaade F, Kristensen KP: Purulent meningitis: a review of 658 cases. Acta Med Scand 171:543-550, 1962 23. Richardson HD, Nakamura S: An electron microscopic study of spinal cord edema and the effect of treatment with steroids, mannitol, and hypothermia. Presented at the 18th Veterans Administration Spinal Cord Injury Conference, Boston, Mass., October 1971 24. Siesj8 BK, SCrenson SC (eds): Ion Homeostasis of the Brain. Proceedings of the Alfred Benzoa Symposium III. New York: Academic Press, 1971 25. Taylor AR, Crockard HA: Monitoring of the cerebral circulation and cerebrospinal fluid chemistry in the management of head injury. Clin Neurosurg 19:121-132, 1972 26. Waggener JD: The animal experimental model: compression injuries. Presented at the International Medical Society of Paraplegia and 19th Veterans Administration Spinal Cord Injury Conference, Scottsdale, Arizona, October 1973 27. Wagner FC Jr, Dohrmann G J, Bucy PC: Histopathology of transitory traumatic paraplegia in the monkey. J Neurosurg 35:272-276, 1971 28. Yashon D, Bingham WG Jr, Faddoul EM, et al: Edema of the spinal cord following experimental impact trauma. J Neurosurg 38:693-697, 1973
This ~vork was supported in part by VA Project 0397-01. Address reprint requests to: Douglas K. Anderson, Ph.D., Veterans Administration Hospital (151B), 13000 North 30th Street, Tampa, Florida 33612.
J. Neurosurg. / Volume 44 /June, 1976
Research Service, Veterans Administration Hospital. and Department of Physiology and Neurology Section, Department of Medicine, University of South Florida College of Medicine, Tampa, Florida v' Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Cat*), magnesium (Mg~+), and chloride (C1) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca ++ concentration on Days 3, 9, 11, 13, and 15, elevation in K + concentration on Days 9 and 11 and decline in C1 levels on the first day. The CSF K + increase probably reflected cellular loss of K* from damaged tissue whereas the Ca ++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury. KEY WORDS 9 spinal cord injury lactate electrolytes
T is now generally agreed that cerebrospinal fluid (CSF) is in direct equilibrium with and reflects the composition of the central nervous system (CNS) extracellular fluid (ECF). 4,7,8 Thus, analysis of C S F can provide an index of C N S metabolism in normal and diseased states. Examination of various CSF components has been used to provide direct diagnosis of a number of clinical conditions, 2t,22 and to determine prognosis of and to guide therapy in cerebral disease or injury? ,12,~8,~8,2~For ex-
I
J. Neurosurg. / Volume 44 / June, 1976
9 cerebrospinal fluid
9
ample, CSF lactate levels are elevated after head injury 3,1~ and may reflect the degree of cerebral damage? 2 With the exception of a study by Bulat, et al., 2 describing a decline in lumbar CSF concentrations of 5-hydroxyindolacetic acid 19 days after spinal cord trauma in cats, no investigative work in this area concerning spinal cord disease or injury has previously been performed. Recent reports of lactate a4 and electrolyte iS alterations in injured spinal cord tissue suggest that CSF analysis following spinal cord 7]5
D. K. Anderson, et al. trauma might be useful in the further study of spinal cord metabolic and/or biochemical changes attending spinal cord injury. The present studies were performed to determine whether experimental spinal cord compression caused significant changes in CSF lactate and electrolyte levels. Methods and Materials
For this study we used immunized and conditioned female mongrel cats ranging in weight from 2.3 to 4.6 kg. They were divided into two groups: one group underwent experimental injury and the other comprised operative controls.
Experimental Injury Animals
intramuscular procaine penicillin (22,000 units/kg) on the day of surgery, and then every other day for 1 week postoperatively. In addition, the animals were given subcutaneous 5% dextrose in Ringer's solution (10 cc/kg) daily postoperatively until they were alert and feeding. With this model, either reversible or irreversible paraplegia can be produced depending upon the magnitude of the weight and the duration of compression. For this study reversible paraplegia was produced by a 5-minute compression with 170-gm weight. The injury was characterized by varied return of weight-bearing and walking 2 to 4 weeks post injury. This magnitude of weight and duration of compression was chosen because it allowed repeated withdrawals of CSF from the lumbar subarachnoid space and eliminated subarachnoid bleeding.
All animals were anesthetized with intraperitoneal (IP) pentobarbital sodium (40 mg/kg) and intubated to maintain a patent airway. A polyethylene cannula was placed in Control Animals the abdominal aorta by way of a femoral In another group of animals designated arteriotomy in order to monitor blood operative controls, all procedures just pressure and to obtain samples for blood gas described were performed with the exception and pH analysis. Ventilation was not assisted of spinal cord compression. unless abnormal blood gas and pH values were obtained. A femoral vein was canCerebrospinal Fluid Sampling nulated for administration of supplemental doses of anesthesia and other drugs as Samples of CSF were obtained from the necessary. Rectal temperature was measured, lumbar subarachnoid space just before and and body temperature maintained between after laminectomy (operative controls) or 36 ~ and 38 ~ C with a heating pad. The cats spinal cord injury (experimental group). were immobilized in a stereotaxic frame, a Postoperative samples in both groups were one-segment laminectomy was performed at obtained at 48-hour intervals starting at 24 L-2, and the epidural fat was removed to ex- hours and continuing for 17 to 21 days. All pose the dura mater. Spinal cord trauma was postoperative CSF samples were obtained induced using a modification of the compres- with the animals lightly anesthetized with insion model described by Waggenexa6 and tramuscular ketamine hydrochloride (10 Richardson and Nakamura. ~8 This method mg/kg). With the animals in a "sphinx-like" involved placing a known weight, ex- position and secured in a stereotaxic frame, tradurally, on the spinal cord for a prescribed the lumbar subarachnoid space was entered length of time. The injury apparatus was a by percutaneous puncture with a shortstainless steel rod (tip, 6 mm in diameter) that beveled No. 20 needle between L-6 and L-7. could be weighed as desired. The rod passed The CSF samples were immediately centhrough a guide tube which was carefully trifuged to remove any blood that might be positioned directly over and perpendicular to present and refrigerated at 4 ~ C until the center of the spinal cord thereby produc- analyzed. It was determined that "slightly ing compression. Succinycholine chloride (1 tinged" CSF samples (hematocrit of 2% or mg/kg) was administered intravenously just less) had no effect on CSF lactate or elecprior to compression to prevent movement trolyte levels if centrifuged immediately. once compression was initiated. All animals Grossly bloody samples were discarded. All were mechanically ventilated during this samples were analyzed within 48 hours for period of muscle paralysis. The wound was lactate, sodium (Na+), potassium (K+), closed in layers and the animals were given calcium (Ca++), magnesium (Mg§ and 716
J. Neurosurg. / Volume 44 / June, 1976
C S F l a c t a t e a n d e l e c t r o l y t e s in c o r d i n j u r y
FIG. 1. Lactate (mg/100 ml, ordinate) concentrations in CSF plotted as a function of days (abscissa) following spinal cord compression (solid line) or laminectomy (broken line). All values are means and vertical bars indicate standard error of the mean (SEM). N = normal (prelaminectomy) or injury CSF lactate concentrations.
chloride (CI). In addition, total protein was analyzed in a limited number of samples. Lactate was determined by the lactate dehydrogenase method, 1 Na +, K +, Ca ++, and Mg §247 by atomic absorbance, C1 by automatic chloride titrator, and protein by the Lowry modification of the FolinCiocalteau procedure? 5
Statistical Analysis All biochemical data obtained were statistically analyzed by the Mann-Whitney U test. Table 1 and Figs. 1 to 4 express the results as group means (as a summary statistic) together with the standard errors of the mean (SEM). A probability of 0.05 was used as the minimum level of significance. Results
Lumbar CSF lactate, Na +, K § Ca ++ , Mg ++, and CI concentrations were determined at 48-hour time intervals for 17 to 21 days following either laminectomy and spinal cord compression (experimental) or laminectomy only (control). Table 1 is a summary of the data appearing in Figs. 1 to 4 for both experimental and control animals. In addition, normal values (means + SEM) for lactate and electrolytes
J. Neurosurg. / Volume 44 / June, 1976
FIG. 2. Sodium (open squares) and chloride (open circles) concentrations (mEq/1, ordinate) in CSF plotted as a function of days (abscissa) post injury (experimental) or laminectomy (control). N = normal CSF sodium and chloride levels.
have been included along with percentage changes from normal at each sampling interval for both control and experimental CSF lactate levels.
Lactate Levels Data reported in Fig. 1 (solid line) and Table 1 reveal significant increases in CSF lactate levels on Days 1 through 9 post injury with peak levels (50% above normal) occurring at Day 5. In control animals (broken line), CSF lactate levels were significantly reduced by 24 hours post laminectomy and remained depressed throughout the 2- to 3-week experimental period. In these cats CSF lactate concentrations were reduced between 15% and 22% below normal (Table 1). There were significant differences between control and experimental CSF lactate concentrations at every sampling interval throughout the experiment.
Electrolyte Levels There was no significant difference between control and experimental CSF Na § levels at any sampling interval throughout the experimental period, although there was a tendency for Na + to be elevated at 11 days post injury (Fig. 2, open squares; Table 1). A
717
D. K. Anderson, et al. TABLE 1
Normal and postinjury CSF lactate and electrolyte values Substance lactate (normal values = ~- SEM) 13.5 • 0.4 N = 27 sodium (normal values • SEM) 157.1 • 0.5 N = 27 chloride (normal values • SEM) 137.9 • 0.3 N = 27 potassium (normal values ~- SEM 2.8 • 0.02 N = 27 calcium (normal values 2~ ~- SEM 2.8 • 0.04 N = 27 magnesium (normal values ~- SEM) 1.9 • 0.02 N = 24
=
Days Postop *
Units
Group
mg/lO0 ml
experimental
1
control mEq/l
experimental control
=
mEq/l
experimental control
=
mEq/1
experimental control
=
mEq/1
experimental control
=
mEq/1
experimental control
3
2~ • SEM ~o change from normal N • SEM change from normal N • SEM N
16.0 • 1.1 18.5 12 10.8 • 0.8 --20.0 5 155.8 • 0.9 11
17.9 • 0.8 32.6 8 10.7 • 0.5 --20.7 6 157.4 • 0.7 5
2~ • SEM N • SEM N
157.8 • 0.2 4 134.4 • 1.0 8
158.4 • 1.3 5 137.2 • 0.9 6
• SEM N • SEM N
139.5 • 0.6 4 2.8 • 0.05 10
137.0 • 0.4 4 3.0 • 0.05 8
• SEM N • SEM N
2.8 • 0.03 4 2.9 • 0.04 10
3.0 • 0.09 5 3.2 • 0.07 7
• SEM N • SEM N
2.9 • 0.09 4 1.9 • 0.04 9
2.9 • 0.06 6 1.9 • 0.04 7
• SEM N
-
1.8 • 0.0 3
* Includes both laminectomy plus injury (experimental) and laminectomy only (controls). All values are means (X) • standard errors of the mean (SEM); N = number of animals.
FIG. 3. P o t a s s i u m c o n c e n t r a t i o n s in ( m E q / l , ordinate) versus days following cord compression (injury) or l a m i n e c t o m y trol). N = p r e i n j u r y or l a m i n e c t o m y potassium values. 718
CSF spinal (conCSF
s i g n i f i c a n t r e d u c t i o n a t 24 h o u r s w a s t h e o n l y d e m o n s t r a b l e c h a n g e in C S F C I levels p o s t i n j u r y ( F i g . 2, open circles; T a b l e 1). Levels of CSF K § were significantly e l e v a t e d a b o v e n o r m a l o n D a y s 3 t h r o u g h 13 p o s t i n j u r y ( F i g . 3, solid line," T a b l e 1). However, CSF K § concentrations from control animals were also significantly elevated o n D a y s 3 t h r o u g h 7 ( F i g . 3, broken line," T a b l e 1) a n d t h e o n l y s i g n i f i c a n t d i f f e r e n c e between experimental and control CSF K § levels o c c u r r e d o n D a y s 9 a n d 11. D a t a r e p o r t e d in Fig. 4 (open squares, solid line) a n d T a b l e 1 d i s c l o s e a s i g n i f i c a n t inc r e a s e in C S F C a +§ levels o n D a y s 3 t h r o u g h 13 p o s t i n j u r y . A l t h o u g h c o n t r o l C S F C a §247 concentrations were slightly elevated on postl a m i n e c t o m y D a y s 3 t h r o u g h 11, n o n e o f t h e s e i n c r e a s e s w e r e s i g n i f i c a n t ( F i g . 4, open
J. Neurosurg. / Volume 44 / June, 1976
CSF lactate and electrolvte8 in cord injury TABLE 1
5
(Continued)
D a y s Postop* 11
7
9
20.1 J: 1.0 48.9 11 10.9 • 0.5
17.8 • 1.0 31.9 10 11.0 • 0.5
17.4 • 1.2 28.9 9 10.6 • 0.4
16.5 • 1.5 22.2 6 11.4 • 0.3
15.4 • 0.8 14.1 7 11.5 • 0.3
13.5 = 0.7 0 5 11.0 • 0.3
-- 19.3
-- 18.5
-- 21.5
-- 15.6
-- 14.8
-- 18.5
5 157.7 • 1.2 12
6 156.9 ~: 1.0 10
6 158.6 • 1.0 9
6 160.6 • 1.4 7
5 158.9 ~: 1.1 7
5 157.0 • 1.1 4
14.6 • 1.0 8.1 3 11.3 • 0.2 - - 16.3 5 158.0 • 0 3
158.0 •
1.9 5 138.0 ~- 1.0 8
155.8 •
1.4 4 138.8 • 1.6 5
157.2 •
1.5 6 138.7 = 0.8 6
157.2 • 1.9 6 139.0 • 1.5 4
156.4 =L 1.4 5 137.8 • 1.3 4
158.0 ~: 1.0 5 139.0 1
157.0 • 1.8 5 138.0 1
138.0 • 0.3 5 2.9 • 0.04 12
137.0 •
3.0 • 0.04 10
139.0 • 0.6 3 3.1 • 0.09 9
138.3 • 0.9 3 3.2 ~= 0.08 7
138.0 =a 0.9 5 3.0 = 0.07 7
138.0 • 0.4 5 2.9 i 0.07 4
138.6 • 0.2 5 3.0 • 0.07 3
3.0 • 0.08 6 3.1 = 0.08 10
2.9 • 0.05 6 3.1 =~ 0.06 10
3.0 =~ 0.05 5 3.1 • 0.07
2.9 • 0.02 5 3.0 • 0.06
2.9 • 0.02 5 2.9 ~ 0.1
3.0 • 0.06 5 3.0 • 0.06
2.9 • 0.07 5 1.9 • 0.04 9
3.0 • 0.09 6 1.9 • 0.06 9
2.9 • 0.06 6 2.0 • 0.05 8
2.9 • 0.08 5 1.9 • 0.04 7
2.8 • 0.04 5 1.8 • 0.06 7
2.6 • 0.05 5 1.9 ~ 0.09 4
2.7 • 0.1 5 1.9 • 0.07 3
2.0 = 0.09 3
1.9 • 0.05 4
2.1 • 0.03 6
2.1 ~- 0.05 5
2.0 • 0.03 5
1.9 • 0.03 5
1.9 ~= 0.02 5
2.9 • 0.1 5 3.0 • 0.07 11
1.2 4
7
13
7
15
4
17
3
squares, broken line).
Significant differences b e t w e e n e x p e r i m e n t a l a n d c o n t r o l C S F C a ++ l e v e l s w e r e n o t e d o n D a y s 3, 9, 11, 13, a n d 15 ( F i g . 4 a n d T a b l e 1). L e v e l s o f C S F M g ++ w e r e n o t s i g n i f i c a n t l y altered at any postinjury sample interval (Fig. 4, open triangles, solid line). H o w e v e r , v a r i a t i o n s in c o n t r o l C S F M g ++ l e v e l s ( F i g . 4, open triangles, broken line) r e s u l t e d in significant elevations of this ion on postlaminectomy D a y s 3 t h r o u g h 13. C o n s e quently, significant differences between control and experimental C S F M g ++ l e v e l s o c c u r r e d o n D a y s 9 a n d 11 ( F i g . 4 a n d T a b l e 1).
Discussion
Lactate Levels Our results demonstrated a significant rise in C S F c o n c e n t r a t i o n s o f l a c t a t e b y 2 4 h o u r s
J. Neurosurg. / Volume 44 /June, 1976
Fro. 4. P o s t i n j u r y C S F c a l c i u m (open squares) a n d m a g n e s i u m (open triangles) c o n c e n t r a t i o n s ! m E q / l , o r d i n a t e ) as a f u n c t i o n o f d a y s f o l l o w i n g injury or l a m i n e c t o m y . N = n o r m a l or p r e s u r g e r y ( l a m i n e c t o m y p l u s c o m p r e s s i o n or l a m i n e c t o m y only.) C S F c a l c i u m a n d m a g n e s i u m c o n c e n trations. 719
D. K. A n d e r s o n , e t al. post injury which remained elevated above normal values for 9 days. The average peak increase in CSF lactate levels occurred at 5 days post injury and thereafter declined toward normal. There is general agreement that: 1) there are considerable blood-brain and blood-CSF barriers to lactate; ~'17'~~ 2) CSF lactate finds its origin in nervous tissue and not in blood; s~ and 3) CSF lactate levels reflect CNS extracellular fluid lactate levels. 1~ Therefore, the increases in CSF lactate seen in this study indicate a shift in injured spinal cord tissue metabolism toward anaerobiosis due to hypoxia. The prolonged elevation of CSF lactate suggests a continuing hypoxia of metabolically active spinal cord tissue for several days post injury. It has been reported that pO2 levels 8'9 decline in injured spinal cord tissue of experimental animals. In addition, a decrease in blood flow through central gray matter of traumatized spinal cord tissue has been demonstrated? ,~ Although not measured in our study, a decrease in blood flow through the injured area (with resulting hypoxia and perhaps also decreased "washout") is probably responsible for the elevated CSF lactate levels observed. The long-term elevation of CSF lactate is at variance with results reported by Locke, et al. TM After a 300-gm-cm impact injury in monkeys, they excised traumatized and nontraumatized (control) segments of spinal cord tissue at nine different time intervals (one monkey/time interval) ranging between 1.5 minutes and 48 hours post injury. These workers demonstrated elevated lactic acid concentrations in traumatized segments of spinal cord for 12 to 18 hours following injury, and concluded that the lactic acid increase presumably resulted from decreased oxygenation and perfusion. At 18 hours post injury, tissue lactate levels approximated control values. The reasons for the discrepancy between our data and those of Locke, et al., 14 might include: 1) different methods of injury, that is, impact versus compression; 2) differences in the magnitude of injury; and 3) species differences. A slight delay between lactate release by hypoxic spinal cord tissue and its appearance in lumbar CSF may occur. This, however, could not account solely for the long-term (9-day) elevation in postinjury CSF lactate levels seen in our study. It has been demonstrated that edema is a secondary posttraumatic complication of ex720
perimental spinal cord injury. 8,18,28 Lewin, et al.? ~ found an increased tissue water content
(edema) 1 day following impact spinal cord trauma in cats. Edema was maximum between Days 3 through 6 and had begun to decline by Day 9. Yashon, et al.? 8 reported evidence of edema 5 minutes after injury which persisted for 15 days reaching a maximum at 5 days following impact trauma to the spinal cord of monkeys. They concluded that since Locke, et al., ~" found evidence of hypoxia (elevated tissue lactate levels) for only 18 hours post injury, long-term edema was due primarily to other factors. Our data imply that posttraumatic hypoxia of the spinal cord is of a long duration. Thus, the long-lasting edema reported by others~8 may be dependent, at least in part, on hypoxia. Taylor and Crockard ~5 indicate that serial CSF lactate levels can rise due to an expanding intracranial hematoma or increasing localized edema following head injury. Since the spinal cord is contained within the relatively inelastic pia mater, it has been proposed that the increased tissue volume raises the pressure on spinal cord tissue resulting in a secondary compression of parenchymal structures. 28 Perhaps edema with resulting compression of spinal tissue vascular elements might contribute to the long-term hypoxia seen in this study. Further investigation of these questions is required before any definitive conclusions can be drawn. The decrease in CSF lactate levels following laminectomy in the control animals was an unexpected, but consistent, finding. Several possibilities could explain this observation. These include: 1) a laminectomyinduced decrease in glucose utilization; 2) increase in oxygen extraction; or 3) increase in spinal cord tissue perfusion that increases "washout" and/or shifts tissue metabolism toward aerobiosis due to increased oxygen delivery to spinal cord tissue. Studies designed to determine which mechanisms are involved are currently in progress in our laboratory. It is hoped that changes in CSF lactate levels will demonstrate a positive correlation with the degree of neurological deficit and return of neurological function in future animal studies and in human patients with spinal cord injuries. Lactate levels in CSF might then be of prognostic value and may J. Neurosurg. / Volume 44 / J u n e , 1976
C S F l a c t a t e a n d e l e c t r o l y t e s in c o r d i n j u r y segments 6 and 9 days following impact injury. They concluded that the K + loss was due to necrotic as well as edematous changes in Electrolyte Levels the injured cord. Thus, the significant CSF The only changes in CSF electrolyte com- K + elevations seen on Days 9 and 11 post inposition that can be attributed to spinal cord jury are probably a reflection of this K § loss trauma p e r se were significant elevations from injured tissue. Correlative histopathological findings in above levels in control animals of Ca ++ concentrations on postinjury Days 3, 9, 11, 13, our laboratory are similar in many respects to and 15, and in K § concentrations on postin- those described in impact injury 5,27 and jury Days 9 and 11. Chloride levels in CSF suggest a common pathogenic mechanism. were significantly reduced below those in con- These findings include hemorrhagic necrosis trol animals at 24 hours post injury. Changes of gray matter, microvacuolation and in CSF electrolytes were minor, amounting to ischemic nerve cell change of anterior horn only a 0.2 to 0.3 m E q / l elevation for K § and cells, "edematous" changes in white matter, Ca § and a 5 mEq/l decline for CI . It may and subsequent cavitation of the spinal cord be that the injured spinal cord segment was involving gray and white matter with relative too small to be reflected in larger alterations sparing of dorsal columns. These histological of CSF electrolyte composition, especially findings will be described in detail in a after dilution within the CSF compartment. separate report. The presence of active clearance mechanisms for K § from the subarachnoid space may Acknowledgments have also played a role in keeping the concenThe authors would like to thank Ms. Dianne tration of this ion near normal values." Kikta, Gail Trocki, and Lisa Kalaf for their It is known that Ca § binds to protein and valuable technical assistance and also Ms. Robin increased Ca §247concentrations have been Scott for typing the manuscript. noted in CSF with elevated protein levels. 2~ While protein levels were not determined in References all samples, periodic analysis revealed that 1. Beutler E: Red Cell Metabolism. A Manual of CSF protein levels were slightly elevated Biochemical Methods. New York: Grune & above normal (60 to 75 mg/100 ml) at various Stratton, 1971, pp 109-111 intervals post trauma. The postinjury eleva2. Bulat M, Lackovi6 Z, Jakup~evi~ M: 5tion of CSF Ca §247may, therefore, be a conhydroxyindoleacetic acid in the lumbar fluid: a sequence of increased CSF protein levels. specific indicator of spinal cord injury. Science Cerebrospinal fluid CI levels can be secon185:527-528, 1974 3. Crockard HA, Taylor AR: Serial CSF lacdarily decreased in the presence of increased tate/pyruvate values as a guide to prognosis in CSF protein 2~or HCO-3? 4 Whether this is the head injury coma, in Fieschi C (ed): Cerebral basis for the decline in CSF C1 concentration Blood Flow and Intracranial Pressure. New at 24 hours post injury is unknown. Perhaps York: S Karger, 1972, pp 533-539 postinjury decline in CSF C1 was due to 4. Davson H: Physiology of the Cerebrospinal other unknown factors. Fluid. Boston: Little, Brown, 1967 Potassium levels in CSF were significantly 5. Ducker TB, Kindt GW, Kempe LG: elevated above normal values on Days 3 Pathological findings in acute experimental through 13 post injury, as were the CSF K + spinal cord trauma. J Neurosurg 35:700-708, concentrations from control animals on Days 1971 6. Ducker TB, Lucas J: Recovery from spinal 3 through 7 post laminectomy. The increase cord injury, in Seeman P, Brown GM (eds): in CSF K + values for the first postoperative Frontiers in Neurology and Neuroscience week in both control and experimental Research. Toronto: University of Toronto animals may have been the result of nonPress, 1974, pp 142-154 specific tissue damage from repeated lumbar 7. Fencl V, Miller TB, Pappenheimer JR: punctures. The only elevations in CSF K + Studies on the respiratory response to disturthat might be attributed to the injury per se bances of acid-base balance, with deductions occurred on Days 9 through 11 post injury. concerning the ionic composition of cerebral Lewin, et al., la found a net loss of K § from interstitial fluid. Am J Physiol 210:459-472, both injured and adjacent spinal cord 1966 provide an index to the efficacy of various therapeutic modalities.
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D. K. Anderson, et al. 8. Katzman R, Pappius HM: Brain Electrolytes and Fluid Metabolism. Baltimore: Williams & Wilkins, 1973 9. Kelly DL Jr, Lassiter KRL, Calogero JA, et al: Effects of local hypothermia and tissue oxygen studies in experimental paraplegia. J Neurosurg 33:554-563, 1970 10. King LR, McLaurin RL, Knowles HC Jr: Acid-base balance and arterial and CSF lactate levels following human head injury. J Neurosurg 40:617-625, 1974 11. Kobrine AI, Doyle TF, Martins AN: Local spinal cord blood flow in experimental traumatic myelopathy. J Neurosurg 42: 144-149, 1975 12. Kurze T, Tranquada RE, Benedict K: Spinal fluid lactic acid levels in acute cerebral injury, in Caveness WS, Walker AE (eds): Head Injury. Philadelphia: JB Lippincott, 1966, pp 254-259 13. Lewin MG, Hansebout RR, Pappius HM: Chemical characteristics of traumatic spinal cord edema in cats. Effect of steroids on potassium depletion. J Neurosurg 40:65-75, 1974 14. Locke GE, Yashon D, Feldman RA, et al: Ischemia in primate spinal cord injury. J Neurosurg 34:614-617, 1971 15. Lowry OH, Rosebrough NJ, Farr AL, et al: Protein measurement with the folin-phenol reagent. J Biol Chem 193:265-275, 1951 16. Moir ATB, Ashcraft GW, Crawford TBB, et al: Cerebral metabolites in cerebrospinal fluid as a biochemical approach to the brain. Brain 93:357-363, 1970 17. Plum F, Posner JB: Blood and cerebrospinal fluid lactate during hyperventilation. Am J Physiol 212:864-870, 1967 18. Posner JB, Plum F: Spinal fluid pH and neurologic symptoms in systemic acidosis. N Engl J Med 277:605-613, 1967 19. Prockop LD: Cerebrospinal fluid lactic acid. Clearance and effect on facilitated diffusion of a glucose analogue. Neurology 18:189-196, 1968 20. Prockop LD: Disorders of cerebrospinal fluid and brain extracellular fluid, in Gaull GE (ed):
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Biology of Brain Dysfunction. New York: Plenum Press, 1973, pp 229-264 21. Prockop LD, Fishman RA: Experimental pneumococcal meningitis. Permeability changes influencing the concentration of sugars and macromolecules in cerebrospinal fluid. Arch Neurol 19:449-463, 1968 22. Quaade F, Kristensen KP: Purulent meningitis: a review of 658 cases. Acta Med Scand 171:543-550, 1962 23. Richardson HD, Nakamura S: An electron microscopic study of spinal cord edema and the effect of treatment with steroids, mannitol, and hypothermia. Presented at the 18th Veterans Administration Spinal Cord Injury Conference, Boston, Mass., October 1971 24. Siesj8 BK, SCrenson SC (eds): Ion Homeostasis of the Brain. Proceedings of the Alfred Benzoa Symposium III. New York: Academic Press, 1971 25. Taylor AR, Crockard HA: Monitoring of the cerebral circulation and cerebrospinal fluid chemistry in the management of head injury. Clin Neurosurg 19:121-132, 1972 26. Waggener JD: The animal experimental model: compression injuries. Presented at the International Medical Society of Paraplegia and 19th Veterans Administration Spinal Cord Injury Conference, Scottsdale, Arizona, October 1973 27. Wagner FC Jr, Dohrmann G J, Bucy PC: Histopathology of transitory traumatic paraplegia in the monkey. J Neurosurg 35:272-276, 1971 28. Yashon D, Bingham WG Jr, Faddoul EM, et al: Edema of the spinal cord following experimental impact trauma. J Neurosurg 38:693-697, 1973
This ~vork was supported in part by VA Project 0397-01. Address reprint requests to: Douglas K. Anderson, Ph.D., Veterans Administration Hospital (151B), 13000 North 30th Street, Tampa, Florida 33612.
J. Neurosurg. / Volume 44 /June, 1976
![[Astroprotein in cerebrospinal fluid following experimental brain injury (author's transl)].](/assets/img/hold.png)
